Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04053634
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : February 28, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 16, 2019
First Posted Date  ICMJE August 12, 2019
Last Update Posted Date February 28, 2020
Actual Study Start Date  ICMJE August 26, 2019
Estimated Primary Completion Date November 22, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2019)
Annualized rate of moderate or severe COPD exacerbations [ Time Frame: Over first 56 weeks ]
Moderate or severe COPD exacerbation is defined by symptomatic worsening of COPD requiring:
  • Use of systemic corticosteroids for at least 3 days; and/or
  • Use of antibiotics; and/or
  • An inpatient hospitalization or death due to COPD
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2019)
  • Annualized rate of severe COPD exacerbations [ Time Frame: Minimum of 1 year and an average of 2 years ]
    A severe COPD exacerbation is defined by symptomatic worsening of COPD requiring an inpatient hospitalization or results in death due to COPD
  • Annualized rate of COPD exacerbations that are associated with an emergency room/emergency department visit or a hospitalization [ Time Frame: Minimum of 1 year and an average of 2 years ]
  • Time to first COPD exacerbation [ Time Frame: During first 56 weeks ]
  • Change from baseline in SGRQ total and domain scores [ Time Frame: up to 56 weeks ]
    St. George's Respiratory Questionnaire (SGRQ)
  • Change from baseline in E-RS:COPD total and domain scores [ Time Frame: up to 56 weeks ]
    Evaluating Respiratory Symptoms in COPD (E-RS:COPD)
  • Change from baseline in pre-dose/pre-bronchodilator FEV1 [ Time Frame: up to 56 weeks ]
    FEV1 is the Forced expiratory volume in one second at study site
  • All cause and respiratory-related mortality rate [ Time Frame: Minimum of 1 year and an average of 2 years ]
  • Annual rate of hospitalizations due to COPD [ Time Frame: Minimum of 1 year and an average of 2 years ]
  • Serum benralizumab concentration as a measure of pharmacokinetics [ Time Frame: up to 56 weeks ]
  • Anti-drug antibodies (ADA) as a measure of immunogenicity [ Time Frame: up to 56 weeks ]
  • Change from baseline in CAT total score [ Time Frame: up to 56 weeks ]
    Chronic Obstructive Pulmonary Disease assessment tool (CAT)
  • Length of hospital stay [ Time Frame: Minimum of 1 year and an average of 2 years ]
  • ICU (Intensive Care Unit) days [ Time Frame: Minimum of 1 year and an average of 2 years ]
  • Annual rate of hospitalizations and emergency department visits combined [ Time Frame: Minimum of 1 year and an average of 2 years ]
  • Annual rate of unscheduled outpatient visits including unscheduled visits to study sites [ Time Frame: Minimum of 1 year and an average of 2 years ]
  • Annual rate of unscheduled healthcare encounters [ Time Frame: Minimum of 1 year and and average of 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 26, 2020)
  • Annualized rate of COPD-related events [ Time Frame: up to 56 weeks ]
    COPD-related event is defined by symptomatic worsening and increase in rescue medication as recorded in the eDiary
  • Severity, frequency and duration of EXACT-PRO defined events [ Time Frame: Up to 56 weeks ]
    Exacerbations of Chronic Pulmonary Disease Tool - Patient Reported Outcome (EXACT-PRO)
  • Clinically important deterioration [ Time Frame: Up to 56 weeks ]
    Clinically Important Deteriorations are defined as
    • 100 mL decrease in pre-dose/pre-bronchodilator FEV1 compared to baseline, •Decline in health-related quality of life (≥4 unit increase in SGRQ total score compared to baseline),
    • 1 moderate or severe on-treatment COPD exacerbation.
  • Onset of effect of benralizumab [ Time Frame: Up to 48 weeks ]
    Patient perception of effect item from the Onset of Effect Questionnaire (OEQ)
  • Total dose and number of days on systemic corticosteroids [ Time Frame: Minimum of 1 year and average of 2 years ]
  • EQ-5D-5L [ Time Frame: Minimum of 1 year and average of 2 years ]
    European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L)
  • Change and percent change from baseline in peripheral blood eosinophil levels [ Time Frame: Minimum of 1 year and average of 2 years ]
    Peripheral blood eosinophil counts
  • Safety and tolerability of benralizumab in patients with moderate to very severe COPD [ Time Frame: Minimum of 1 year and average of 2 years ]
    AEs, vital signs, clinical laboratory, and ECG
  • Total rescue medication use [ Time Frame: Minimum of 1 year and average of 2 years ]
Original Other Pre-specified Outcome Measures
 (submitted: August 9, 2019)
  • Annualized rate of COPD-related events [ Time Frame: up to 56 weeks ]
    COPD-related event is defined by symptomatic worsening and increase in rescue medication as recorded in the eDiary
  • Severity, frequency and duration of EXACT-PRO defined events [ Time Frame: Up to 56 weeks ]
    Exacerbations of Chronic Pulmonary Disease Tool - Patient Reported Outcome (EXACT-PRO)
  • Clinically important deterioration [ Time Frame: Up to 56 weeks ]
    Clinically Important Deteriorations are defined as
    • 100 mL decrease in pre-dose/pre-bronchodilator FEV1 compared to baseline, •Decline in health-related quality of life (≥4 unit increase in SGRQ total score compared to baseline),
    • 1 moderate or severe on-treatment COPD exacerbation.
  • Onset of effect of benralizumab [ Time Frame: Up to 48 weeks ]
    Patient perception of effect item from the Onset of Effect Questionnaire (OEQ)
  • Total dose and number of days on systemic corticosteroids [ Time Frame: Minimum of 1 year and average of 2 years ]
  • EQ-5D-5L [ Time Frame: Minimum of 1 year and average of 2 years ]
    European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L)
  • Change and percent change from baseline in peripheral blood eosinophil levels [ Time Frame: Minimum of 1 year and average of 2 years ]
    Peripheral blood eosinophil counts
  • Safety and tolerability of benralizumab in patients with moderate to very severe COPD [ Time Frame: Minimum of 1 year and average of 2 years ]
    AEs, vital signs, clinical laboratory, and ECG
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab 100 mg in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent COPD Exacerbations and Elevated Peripheral Blood Eosinophils (RESOLUTE)
Brief Summary

Phase 3 study to evaluate the efficacy and safety of a benralizumab in patients with moderate to very severe COPD with a history of frequent COPD exacerbations and elevated peripheral blood eosinophils (≥300/μL).

Eligible patients must have a history of ≥2 moderate and/or severe COPD exacerbations in the previous year despite receiving triple (ICS/LABA/LAMA) background therapy. Eligible patients must also have an elevated blood eosinophil count.

The treatment period will be of variable duration and will continue until the last patient has the opportunity to complete a minimum of 56 weeks, at which point all patients will complete the study. The primary endpoint will be analyzed at Week 56.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Obstructive Pulmonary Disease
Intervention  ICMJE
  • Biological: Benralizumab
    Benralizumab solution for injection in accessorized prefilled syringe (APFS) will be administered subcutaneously (SC) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks until the end of treatment.
  • Biological: Placebo
    Matching placebo will be administered subcutaneously with accessorized prefilled syringe (APFS) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks until the end of treatment.
Study Arms  ICMJE
  • Experimental: Benralizumab
    Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks
    Intervention: Biological: Benralizumab
  • Placebo Comparator: Placebo
    Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 9, 2019)
868
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 22, 2023
Estimated Primary Completion Date November 22, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provision of informed consent
  2. Age 40 to 85 years
  3. Male and/or female.
  4. Current or former smoker with a tobacco history of ≥10 pack-years.
  5. History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC<0.70 and FEV1 ≤65% of predicted normal value.
  6. Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment.

    1. Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization.
    2. Hospitalization is defined as an inpatient admission ≥24 hours
    3. Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD.
  7. Documented use of triple (ICS/LABA/LAMA) background therapy for COPD throughout the year (52 weeks) prior to enrollment.

    1. ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily.
    2. Total cumulative duration of not being on triple background therapy must not exceed 2 months.
    3. Stable therapy/doses for the last 3 months prior to randomization.
  8. Blood eosinophil count ≥300/μL at screening and documented historical eosinophil count of ≥150/μL within 52 weeks of enrollment (or repeated testing during run-in).
  9. CAT total score ≥15 at Visit 1.
  10. Negative pregnancy test for females of childbearing potential (WOCBP) at Visit 1.
  11. Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control from enrollment throughout the study and within 12 weeks after last dose of IP.

Women not of childbearing potential are defined as women who are either permanently sterilized or postmenopausal (confirmed by FSH test for women <50 years).

Exclusion Criteria:

  1. Clinically important pulmonary disease other than COPD
  2. Current diagnosis of asthma, prior history of asthma or asthma-COPD overlap according to GINA/GOLD. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18.
  3. Radiological findings of a respiratory disease other than COPD contributing to respiratory symptoms. Solitary pulmonary nodules without appropriate follow up or findings of acute infection.
  4. Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
  5. Any unstable disorder that could affect patient safety, study findings or the patient's ability to complete the study.
  6. Any clinically significant abnormal findings in physical examination, vital signs, ECG, laboratory tests could affect patient safety, study findings or the patient's ability to complete the study.
  7. Cor pulmonale and/or right ventricular failure.
  8. Long-term treatment with oxygen >4.0 L/min and/or oxyhemoglobin saturation <89% while breathing supplemental oxygen.
  9. Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed.
  10. Known immunodeficiency disorder, including positive HIV-1/2 testing.
  11. Active liver disease. Chronic stable hepatitis B and C (including positive HBsAg or hepatitis C antibody testing), or other stable chronic liver disease are acceptable.
  12. ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during the run-in period.
  13. Helminth parasitic infection within 24 weeks prior to enrollment, not treated or failed to respond to standard of care therapy.
  14. Alcohol or drug abuse within the past year, which may compromise the study data.
  15. Malignancy, current or within the past 5 years, except for adequately treated non invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than 1 year prior to Visit 1. Suspected malignancy or undefined neoplasms.
  16. Evidence of active tuberculosis, as judged by investigator. Patients with a recent (within 2 years) first-time or newly positive PPD or Quantiferon test need to complete an appropriate course of treatment before enrollment. Evaluation will be according to the local standard of care.
  17. Participation, or planned participation, in intensive COPD rehabilitation program (maintenance phase of a rehabilitation is allowed).
  18. History of surgical or endoscopic lung volume reduction within the 6 months prior to enrollment. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
  19. Scheduled major surgical procedure during the study. Minor elective procedures are allowed.
  20. History of anaphylaxis to benralizumab or any other biologic therapy.
  21. Receipt of blood products or immunoglobulins within 30 days prior to randomization.
  22. Receipt of any marketed or investigational biologic product within 4 months or 5 half-lives prior to randomization, whichever is longer.
  23. Receipt of live attenuated vaccines 30 days prior to randomization.
  24. Chronic use of immunosuppressive medication or expected need for chronic use during the study.
  25. Chronic use of antibiotics if duration of treatment is <9 months prior to randomization. Chronic macrolide or other antibiotic therapy is allowed provided the patient has been on stable dose/regimen for ≥9 months prior to randomization and has had ≥2 COPD exacerbations while on stable therapy.
  26. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to enrollment.
  27. Receipt of benralizumab within 12 months prior to enrollment.
  28. Known history of allergy or reaction to any component of the IP formulation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Brazil,   Canada,   Chile,   Colombia,   Czechia,   Denmark,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Philippines,   Poland,   Spain,   Sweden,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04053634
Other Study ID Numbers  ICMJE D3251C00014
2019-001800-39 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gerard Criner, MD Temple University School of Medicine, 3401 North Broad Street, Suite 745 PP, Philadelphia, PA 19140
PRS Account AstraZeneca
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP